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IFN-γ regulates CD8(+) memory T cell differentiation and survival in response to weak, but not strong, TCR signals

Item Type:Article
Title:IFN-γ regulates CD8(+) memory T cell differentiation and survival in response to weak, but not strong, TCR signals
Creators Name:Stoycheva, D. and Deiser, K. and Stärck, L. and Nishanth, G. and Schlüter, D. and Uckert, W. and Schüler, T.
Abstract:In response to primary Ag contact, naive mouse CD8+ T cells undergo clonal expansion and differentiate into effector T cells. After pathogen clearance, most effector T cells die, and only a small number of memory T cell precursors (TMPs) survive to form a pool of long-lived memory T cells (TMs). Although high- and low-affinity CD8+ T cell clones are recruited into the primary response, the TM pool consists mainly of high-affinity clones. It remains unclear whether the more efficient expansion of high-affinity clones and/or cell-intrinsic processes exclude low-affinity T cells from the TM pool. In this article, we show that the lack of IFN-gammaR signaling in CD8+ T cells promotes TM formation in response to weak, but not strong, TCR agonists. The IFN-gamma-sensitive accumulation of TMs correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62LhiBcl-2hiEomeshi TMPs. Reconstitution of mammalian target of rapamycin or IFN-gammaR signaling is sufficient to block this process. Hence, our data suggest that IFN-gammaR signaling actively blocks the formation of TMPs responding to weak TCR agonists, thereby promoting the accumulation of high-affinity T cells finally dominating the TM pool.
Keywords:Antigen T-Cell Receptors, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Survival, Immunologic Memory, Interferon-gamma, Interferon Receptors, L-Selectin, Knockout Mice, Proto-Oncogene Proteins c-bcl-2, Signal Transduction, T-Box Domain Proteins, TOR Serine-Threonine Kinases, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:553-559
Date:15 January 2015
Official Publication:https://doi.org/10.4049/jimmunol.1402058
PubMed:View item in PubMed

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